title: Autophagy: a pathway that contributes to connexin degradation.
abstract: The function of connexins, which form gap junctions, can be rapidly modulated by degradation, because they have half-lives of only a few hours. Autophagy is a degradation pathway that has been implicated in several diseases and can be induced by cellular stresses such as starvation. We investigated the involvement of autophagy in proteolysis of the wild-type connexins CX50 and CX43, and a cataract-associated connexin mutant, CX50P88S, which forms cytoplasmic accumulations. We observed that cytoplasmic connexins were partially (cup-shaped) or completely (ring-shaped) enclosed by structures containing the autophagy-related protein LC3. Intracellular connexins also colocalized with p62, a protein that might serve as a cargo receptor for autophagic degradation. Starvation induced a decrease in connexin levels that was blocked by treatment with chloroquine, a lysosomal protease inhibitor, or by knockdown of the autophagy-related protein Atg5. These results demonstrate that autophagy can regulate cellular levels of wild-type connexins and imply that the persistence of accumulations of CX50P88S results from insufficient degradation capacity of constitutive autophagy.
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lichtenstein
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Minogue
authors.forename: Eric C
authors.initials: EC
authors.lastname: Beyer
authors.forename: Viviana M
authors.initials: VM
authors.lastname: Berthoud
mesh_terms: D000818:Animals; D001343:Autophagy; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D000099264:Connexin 50
chemical_list: D018031:Connexin 43; D017630:Connexins; D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; D000099264:Connexin 50; C477012:MAP1LC3A protein, human